Table 1.

Modeling diseases of microvascular dysfunction using vascularized microfluidics

	Characteristics of perfusate, blood, and/or blood cells	Vascular and endothelial cell type(s)	Affected organ(s)	Functional capabilities
Coronary microvascular disease	Depends on specific experiment	Coronary microvascular endothelial cells, smooth muscle cells	Heart	Vasospasm, endothelial dysfunction, microvascular obstruction, varied shear rates
Cerebral amyloid angiopathy	Deposition of amyloid beta on endothelial cells, inclusion of anticoagulant medications in perfusate/blood	Brain microvascular endothelial cells, smooth muscle cells	Brain	Vasospasm, microvascular obstruction, microvascular hemorrhage, varied shear rates, protein deposition
Diabetic microvascular disease	Elevated glucose in perfusate/blood, advanced glycation end products, inflammatory mediators (e.g., cytokines)	Microvascular endothelial cells of the target organ, smooth muscle cells (depending on type of experiment)	Classically, eye (retina), kidney, and peripheral nerves, but also skin, brain, adipose tissue, and cardiac and skeletal muscle	Endothelial dysfunction, vasospasm, thrombosis, varied shear rates
Sepsis and disseminated intravascular coagulation	Depending on severity: increased white blood cell count; decreased platelet count; elevated glucose, creatinine, liver enzymes, or serum lactate; decreased coagulation factors (longer clotting times)	Microvascular endothelial cells of the target organ, white blood cells (mononuclear cells)	Lung and kidneys, followed by brain, heart, liver, spleen, adrenal glands, pancreas, and gastrointestinal tract	Endothelial dysfunction, vasospasm, thrombosis, hemorrhage, varied shear rates
Thrombotic microangiopathies	HUS: Shiga toxin; aHUS: complement activation; TTP: ADAMTS13 deficiency; HELLP: unknown	Microvascular endothelial cells of the target organ (e.g., kidney glomerulus)	HUS: kidney; TTP: kidney, heart, brain; HELLP: liver	Endothelial dysfunction, vasospasm, thrombosis, hemorrhage, varied shear rates
Sickle cell disease	Blood or red blood cells from sickle cell disease patients or transgenic murine models, leukocytes, and platelets activated due to inflammatory conditions	Microvascular endothelial cells of the target organ (i.e., lung, kidney, brain)	All but lung, kidney, and brain are of specific interest	Endothelial dysfunction, thrombosis, in vitro sickle cell vaso-occlusion, varied shear rates, varied oxygen levels ranging from hypoxia to normoxia
Acute respiratory distress syndrome	Neutrophils activated with inflammatory mediators	Pulmonary microvascular endothelial cells	Lung	Endothelial dysfunction, thrombosis, neutrophil retention, and microvascular occlusion, varied shear rates
Cancer	Increased angiogenic factor stimulators; decreased inhibitors, vascular endothelial growth factor gradient, circulating cancer, and endothelial progenitors	Microvascular endothelial cells of the target organ, pericytes, platelets, macrophages, endothelial progenitor cells, tumor initiating cells, and more (11)	All, depending on cancer type and location	Endothelial remodeling, thrombosis, permeability, hypoxia, varied shear rates
Psoriasis/rheumatoid arthritis	Microvascular endothelial cells of the target organ, smooth muscle cells, specialized postcapillary venules, lymphocytes, polymorphonuclear cells	Psoriasis: angiogenic factors (112); rheumatoid arthritis: synoviocyte secreted IL-1, IL-6, TGF-β, IL-8, C5a, leukotriene B4 (122)	Papillary dermis (psoriasis), synovium (rheumatoid arthritis)	Endothelial remodeling, thrombosis, immune cell trafficking, varied shear rates

All vessels of the microvasculature (capillaries, prearterioles, arterioles, and venules) are implicated in these diseases. Abbreviations: aHUS, atypical hemolytic uremic syndrome; HELLP, hemolysis, elevated liver enzymes, and low platelet count; HUS, hemolytic uremic syndrome; TTP, thrombotic thrombocytopenic purpura.